Platelet α2-adrenergic receptors density in hypercholesterolemia. Relationship with platelet sensitivity to epinephrine

Aim of the study was to assess whether platelet hyperaggregation to epinephrine, frequently observed in hypercholesterolemia is associated with an increase of alfa2-adrenoceptor density and/or affinity for epinephrine. Thus, platelet aggregation and binding studies, using [3H]yohimbine as ligand, were performed on platelets isolated from 30 type Ila hypercholesterolemic patients (HC) and 23 controls. Platelet aggregation to epinephrine, evaluated as AC50, was significantly higher in HC than in controls (0.9±1vs 0.4±0.3 µg/ml p<0.01). A significant increase of alfa2-adrenoceptor density (Bmax) was observed in a subgroup of 13 HC patients, compared to 13 sex and age matched controls (280±61 and 230±49 fmol/mg prot., respectively, p<0.03). In addition, In this subgroup, an inverse correlation between platelet aggregation and plasma total (r=-0.39, p<0.05) and LDL-cholesterol levels was found (r=-0.38, p<0.05), concomitantly with a direct correlation between platelet receptor density and total and low density lipoprotein cholesterol (r=0.54; p<0.01 and r-0.44; p<0.05). In conclusion our results indicate that platelet alfa2-receptor density is increased in hypercholesterolemia and that plasma and LDL-cholesterol levels significantly correlate with platelet alfa2-receptor density. These findings explain, at least In part, the enhanced platelet response to epinephrine observed in hypercholesterolemia.